298例骨髓增生异常综合征患者染色体核型与临床预后分析

Analysis of the karyotype abnormalities and its prognostic in 298 patients with myelodysplastic syndrome

目的探讨骨髓增生异常综合征（MDS）患者的细胞遗传学特点及其与MDS诊断分型、疾病进展和预后的关系。方法回顾性分析2008年6月至2013年10月浙江大学医学院附属第一医院收治的298例MDS患者的临床特征及预后情况，随访观察并进行相关性研究。结果难治性血细胞减少伴单系发育异常（RcuD）18例，难治性贫血伴环状铁粒幼红细胞（RARs）8例，难治性血细胞减少伴多系发育异常（RCMD）104例，难治性贫血伴原始细胞过多（RAEB）-176例，RAEB-285例，MDS不能分类5例，单纯del（5q）2例。染色体异常检出率39．6％，单纯数目异常45例，单纯结构异常31例，42例两种异常同时存在，均为不平衡易位及复杂异常。RAEB组（RAEB-1＋RAEB-2）染色体异常检出率及复杂染色体异常检出率均高于非RAEB组（RARS＋RCMD＋RCUD）（47．2％对29．2％，P=0，002）。根据IPSS．R积分系统分组，除极低危组外，随着危险分层的递增，染色体异常检出率逐渐增加（P〈0．05），且随着IPSS．R积分越高，转化为白血病的概率越高（P〈0．01）。＋8染色体异常占所有核型异常的19．5％，在RAEB组＋8染色体异常组2年总生存率低于正常染色体组（43％对68％，P=0．005）。结论染色体核型分析是MDS患者判断预后的一个独立因素，对于MDS的诊断、治疗方案的制定及预后判断均有较大意义，＋8染色体异常作为中等预后的染色体异常，在RAEB组预后差于正常染色体核型。

Objective To investigate the relationship between cytogenetic markers with World Health Organization （WHO） classification, disease progress and prognosis in cases with primary myelodysplastic syndromes （MDS）. Methods 298 patients with de novo MDS from the first affiliated hospital of medical school, Zhejiang University were enrolled in the retrospective analysis of WHO classification, karyotype, and prognosis. Follow-up study was also conducted. Results The WHO classifications at first diagnosis were as follows： refractory cytopenia with unilineage dysplasia （RCUD）, 18 cases; refractory anemia with ring sideroblasts （RARS）, 8 cases; refractory cytopenia with multiline dysplasia （RCMD）, 104 cases; refractory anemia with excess blasts- 1, 76 cases; refractory anemia with excess blasts-2, 85 cases; MDS unclassified （MDS-U）, 5 cases involved; and single del （5q）, 2 cases. 39.6% of MDS patients carried karyotypic abnormalities. Among them, the frequency of numerical abnormalities, structural abnormalities and the existence of composite abnormalities were 45, 31, and 42, respectively. The composite abnormalities were unbalanced translocations and complex chromosomal abnormalities. The incidence of both karyotypic abnormalities and complex chromosomal abnormalities inRAEB group was higher than that in non-RAEB group （P〈0. 05）. An analysis based on IPSS-R Scoring System showed that advanced risk stratification （except the low-risk group） gradually enhanced the incidence of karyotypic abnormalities （P〈0.05）. In addition, the probability of evolution to leukemia increased with the higher IPSS-R score （P〈0.05）. In RAEB group, the cases with ＋ 8 chromosome, accounting for 19.5% of karyotypic abnormalities, had worse prognosis than those with normal chromosomes. Conclusions Karyotype was identified with an independent risk factor in MDS patients. Therefore, the information on cytogenetic analysis was critical for diagnosis, prognosis and individual treatment. MDS patients presenting＋8 chromosome, an intermediate risk factor, were associated with a poorer outcome compared to cases with normal chromosomes in RAEB group.